Ubiquitin Specific Protease 11 (USP11), USP4 and USP15 are highly conserved and are characterised by an N-terminal 'domain present in ubiquitin specific proteases' (DUSP) and 'ubiquitin-like' (UBL) domains. This DUSP-UBL (DU) domain is thought to be involved in substrate recognition. It was shown that USP11 co-purifies with human Polycomb Repressive Complex type 1 (PRC1) and regulates the stability of the E3 ligase component of PRC1 (Maertens et al, 2010). PRC1 repress transcription from the INK4a tumour suppressor locus. Hence knockdown of USP11 in primary human fibroblasts causes de-repression of INK4a, followed by a senescence-like proliferative arrest. In this project we aimed to map the interaction between USP11 and PRC1 components (BMI1, RING2, MEL18 and CBX8). We used two methods to investigate their interactions; yeast two-hybrid and in vitro pull down. Unexpectedly, we could not confirm a direct interaction between USP11 and any PRC1 component. We hypothesize that the lack of post-translation modifications, the presence of fusion tags and/or the need of a multi-subunit PRC1 complex might be needed to observe a high affinity interaction. We also aimed to map the interaction between three PRC1 components; RING2, BMI1 and RYBP, with the ultimate aim of solving the X-ray structure of the complex. The main obstacle in this project was to express, extract and purify these proteins at high levels in bacterial culture. Preliminary data suggests that RYBP and BMI1 do not interact directly. Here we report the 3.6 Å resolution X-ray structure of the human USP11 DU. The sequence linking the DUSP and UBL domains, the DU finger, could not be assigned in the electron density map due to low resolution. Comparison with the related USP4 DU crystal structure reveals that the structures are mostly conserved.